The sparse human population of 22 000 is 60% aboriginal. Water access dictated the location of most communities in the Taiga Plains Ecozone. As a result, many are found in ecologically rich valleys and estuaries. Even the largest towns, such as Fort Nelson in British Columbia (3 804 residents) and Inuvik in the Northwest Territories (3 178), are immediately adjacent to vast tracts of pristine land. The few all-weather roads reach every community with a population over 1 000 persons, such as Hay River, Fort Smith, and Fort Simpson, all in the Northwest Territories.

Relatively few areas in the Taiga Plains are dominated by human activity. Much of the local economy is based on subsistence hunting, trapping, and fishing. However, the economy does include a small number of industrial activities such as mining, petroleum extraction, and, in recent years, forestry.

Fossil fuel reserves in the Mackenzie Valley are currently being exploited at the Pointed Mountain and Kotaneelee gas fields, located on the Liard Plateau, and at the Norman Wells oil field, which is Canada's fourth-largest producer.